Depletion of SLC7A11 Sensitizes Nasopharyngeal Carcinoma Cells to Ionizing Radiation.

BACKGROUND: Radiotherapy is the primary treatment choice for Nasopharyngeal Carcinoma (NPC). However, its efficacy is compromised due to radioresistance. Ferroptosis, a novel iron-dependent regulated cell death induced by Ionizing Radiation (IR), plays a role in promoting cancer cell death. Yet, the relationship between enhanced ferroptosis and increased sensitivity of NPC cells to IR remains poorly understood. OBJECTIVE: This study aimed to explore the association between IR and ferroptosis in NPC, as well as the role of the ferroptosis repressor SLC7A11 in IR-treated NPC cells. METHODS: CNE1 and HNE-2 NPC cells were subjected to IR treatment. We performed qPCR and western blotting to evaluate the expression of ferroptosis-related genes in both control and IR-treated NPC cells. Additionally, we used the MTT assay to measure the viability of these NPC cells. JC-1 and DCFH-DA staining were employed to assess mitochondrial membrane potential and Reactive Oxygen Species (ROS) levels in both control and IR-treated NPC cells. Furthermore, we examined the levels of Fe2+, Malondialdehyde (MDA), reduced Glutathione (GSH), and oxidized glutathione (GSSG) in these cells. Moreover, we depleted SLC7A11 in IR-treated NPC cells to investigate its impact on the ferroptosis of these cells. RESULTS: IR upregulated the expression of ferroptosis-related genes, including SLC7A11, ACSL4, COX2, FTH1, and GPX4, in CNE1 and HNE-2 cells. IR treatment also resulted in decreased cell viability, disrupted mitochondrial membrane potential, increased ROS levels, altered glutathione levels, and elevated Fe2+ levels. Knockdown of SLC7A11 enhanced the sensitivity of NPC cells to IR. CONCLUSION: IR may induce ferroptosis in NPC cells, and stimulating ferroptosis could potentially serve as a therapeutic strategy to enhance the efficacy of IR in treating NPC patients.

Horizontal middle partial laryngectomy with cricothyroidopexy: an effective treatment for stage T1b glottic carcinoma.

BACKGROUND: The current treatment options for T1b glottic carcinoma often lead to poor treatment outcomes or voice quality. OBJECTIVES: This study evaluates the therapeutic efficacy of horizontal middle partial laryngectomy with cricothyroidopexy (HMPL-CTP) for stage T1b glottic carcinoma. MATERIAL AND METHODS: A retrospective analysis was conducted on 73 patients with T1b glottic carcinoma. The patients were categorized into three groups: Group A (n = 22) underwent transoral laser microsurgery (TLMS), Group B (n = 21) received frontolateral vertical partial laryngectomy (FVPL), and Group C (n = 30) underwent HMPL-CTP. The study analyzed the 5-year overall survival rate (OS), recurrence rate, phonatory status, and incidence of laryngeal stenosis. RESULTS: Voice quality scores varied significantly in the three groups, while the 5-year OS were similar. The local recurrence rate is higher in Group A than in the other two groups. The laryngeal stenosis rate in Group B is higher than in Groups A and C. Adhesions in the anterior commissure were observed in 18 cases in Group A and nine cases in Group C. CONCLUSIONS AND SIGNIFICANCE: HMPL-CTP demonstrates efficacy as a treatment for stage T1b glottic carcinoma, offering favorable preservation of laryngeal function and minimal complications.

Prognostic significance of residual or recurrent lymph nodes in the neck for patients with nasopharyngeal carcinoma after radiotherapy.

BACKGROUND: Nasopharyngeal carcinoma is the most frequently diagnosed primary tumor originating from the nasopharynx, and the preferred treatment modality is radiotherapy. AIMS: To identify nasopharyngeal carcinoma prognostic factors in patients with residual or recurrent cervical lymph node metastases after radiotherapy. PATIENTS AND METHODS: The clinicopathologic characteristics and prognoses of 67 nasopharyngeal carcinoma patients with residual or recurrent cervical lymph node metastases who were diagnosed and treated were analyzed retrospectively. The Chi-squared test and Cox proportional hazard regression model were used to investigate associations between survival and clinicopathological features. Cumulative survival plots were obtained using the Kaplan-Meier method. RESULTS: Data analysis using the Cox proportional hazard regression model revealed that the size of residual or recurrent lymph node metastases, level V lymph node involvement, number of involved levels, surgical procedure performed, and distant metastases were significantly associated with overall survival. Chi-squared analysis only determined a significant correlation between distant metastases and patient survival. Furthermore, the Kaplan-Meier analysis demonstrated that the 1-, 3-, and 5-year survival rates for patients were 86.6%, 52.2%, and 38.6%, respectively. Radical neck dissection resulted in substantially longer overall survival than modified neck dissection. CONCLUSION: The size of residual or recurrent lymph node metastases, level V lymph node involvement, number of involved levels, surgical procedure performed, and presence of distant metastases were prognostic factors for nasopharyngeal carcinoma patients with residual or recurrent cervical lymph node metastases after radiotherapy, with distant metastases being the most important determinant. Classical radical neck dissection is recommended for treating recurrent nodal disease in nasopharyngeal carcinoma.

RNF8 plays an important role in the radioresistance of human nasopharyngeal cancer cells in vitro.

Tumor residue or recurrence is common after radiation therapy for nasopharyngeal cancer (NPC) since the tumor cells can repair irradiation-induced DNA damage. The ubiquitination cascade mediates the assembly of repair and signaling proteins at sites of DNA double-strand breaks (DSBs). Ring finger protein 8 (RNF8) is an E3 ubiquitin ligase that triggers ubiquitination at the site of DSBs. The present study aimed to identify whether and how RNF8 small interfering RNA (siRNA) treatment enhances the radiosensitivity of irradiated human NPC cell lines. The CNE1, CNE2, and SUNE human NPC cell lines were stably transfected with a constructed RNF8-targeting siRNA expression vector. Western blotting was used to detect the effectiveness of RNF8 downregulation by RNF8 siRNA. The siRNA-transfected (RNF8-) and non-transfected (RNF8+) cells were irradiated at different doses by a linear accelerator. The growth inhibition ratio and apoptosis rate were detected by the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. The ataxia-telangiectasia mutated (ATM), DNA-PKcs, Chk1, Chk2, Nbs1 and Ku80 protein levels in each group were determined. The growth inhibition ratio and apoptotic percentage of RNF8- cells were higher than those of the RNF8+ cells in each of the three cell lines. Lower protein expression levels of Chk1, Chk2, ATM, and Nbs1 were observed in the irradiated RNF8- cells compared to the irradiated RNF8+ cells in each of the three cell lines (P<0.01). As a result, a conclusion could be drawn that RNF8 recruits and ubiquitinates many factors to repair DNA damage, including DSBs, thereby conferring radioresistance to NPC cells.

[Research on apoptosis changes of tensor veli palatini in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore apoptosis changes of dilator muscles in the upper airway by detecting the expression of Bax, Bcl-2 in tensor veli palatini in patients with OSAHS. METHOD: The expression of Bax and Bcl-2 were detected in tensor veli palatini in 30 cases with OSAHS and 10 cases chronic tonsillitis without OSAHS by immunohistochemistry and image analytical system, and the results were analyzed. RESULT: (1) The expression levels of Bax in the OSAHS group increased significantly compared to control group (P < 0.05), but there were no significant differences of Bcl-2 expression between two groups, the ratio of Bax/Bcl-2 increased significantly (P < 0.05). (2) There were positive correlations between AHI and the expression levels of Bax (r = 0.697, P < 0.01) respectively in the test group. CONCLUSION: The results indicate that apoptosis occurred in tensor veli palatini in patients with OS AHS, and the more severity of OSAHS, the more apoptosis.